Biomedical subjects

I Feinberg

Publications and source records attributed to I Feinberg.

94 records · Page 6Linked to original sources

PubMedDate not supplied

Observations on delta homeostasis, the one-stimulus model of NREM-REM alternation and the neurobiologic implications of experimental dream studies.

We first review the concept of delta homeostasis as formulated in our 1974 model and as developed quantitatively by Borbely and colleagues in several versions of the two-process model. We illustrate difficulties in the application of this quantitative model to the negative delta rebound in the rat and we put forward additional evidence that the negative rebound is a pathological rather than a homeostatic response to sleep deprivation. We next review experiments on rats in which the waking metabolic rate of limbic structures was increased by blockade of the NMDA-gated cation channel with ketamine and MK-801. As predicted by the 1974 homeostatic model, NREM delta increased during subsequent sleep. However, it remains to be shown that this powerful effect is actually caused by the metabolic change and that it is an intensification of physiological sleep rather than a non-specific increase in EEG slow waves caused by neurotoxicity. We then outline our one-stimulus model of NREM/REM alternation. In this model NREM sleep is induced by periodic (neuroendocrine?) pulses. These pulses increase delta EEG amplitude and density, depress arousal level and inhibit neural activity. When the strength of the pulsatile stimulus falls below a critical level, REM emerges as neuronal escape. Last, we discuss the neurobiologic implications of two robust findings in experimental dream studies: the relation of dream reports to arousal and the consistent failure of controlled studies to demonstrate qualitative differences between NREM and REM mentation.

Animals↗

PubMedDate not supplied

Independence of sleep EEG responses to GABAergic hypnotics: biological implications.

GABAergic hypnotics are known to depress non-rapid eye movement delta and rapid eye movements and to stimulate non-rapid eye movement sigma (spindles) and beta EEG. This study addressed the question of whether the magnitudes of these effects are significantly correlated. Data were from a study in 16 normal subjects whose sleep was recorded for five nights under placebo and for three nights each under zolpidem (10 mg), triazolam (0.25 mg) and temazepam (30 mg). EEG was analyzed with both period-amplitude and power spectral (FFT) analysis. The magnitudes of the EEG and eye movement density responses were not significantly correlated for any of the three drugs. It is therefore unlikely that sleep responses to GABAergic drugs can be explained by the common cellular action (increased chloride conductance) of these drugs. We suggest that the sleep EEG responses are manifestations of complex (but consistent) interactions of excitation and inhibition in large brain systems although certain aspects of these responses (e.g. the different time courses of delta vs sigma and eye movement responses) may reflect molecular adaptations. A separate observation in this study was the strong traitlike characteristics of the sleep variables studied. These variables were highly correlated across nights of baseline sleep; in addition, individual differences in baseline sleep were significantly retained on the third night of temazepam administration.

Adult↗

PubMedDate not supplied

Effects of hypnotics on the sleep EEG of healthy young adults: new data and psychopharmacologic implications.

Benzodiazepine hypnotics increase NREM sleep and alter its EEG by reducing delta (0.3-3 Hz) and increasing sigma (12-15 Hz) and beta (15-23 Hz) activity. We tested whether the nonbenzodiazepine hypnotic, zolpidem (10 mg), produced the same pattern of sleep and EEG changes as two "classical" benzodiazepines, triazolam (0.25 mg) and temazepam (30 mg). Sleep EEG of 16 subjects was analyzed with period amplitude analysis for 3 nights during drug administration or placebo. The effects of zolpidem were in the same direction but generally of smaller magnitude than those of the classical benzodiazepines. These differences are more likely the result of non-equivalent dosages than different pharmacologic actions. Period amplitude analysis showed that the decreased delta activity resulted mainly from a decrease in wave amplitude. In contrast, the increased sigma and beta activity were produced by increased wave incidence. Delta suppression increased with repeated drug administration but sigma and beta stimulation did not. While these findings have little relevance for the clinical choice of hypnotics they may hold important implications for the brain mechanisms involved in hypnotic tolerance and withdrawal delirium.

Adult↗

PubMedDate not supplied

The impact of clozapine treatment on serum lipids in chronic schizophrenic patients.

The aim of this retrospective study is to determine whether lipid levels rise in neuroleptic-resistant chronic schizophrenic patients during clozapine treatment and if this rise is correlated with a decrease in aggressive and suicidal behavior. Seventy neuroleptic-resistant schizophrenic patients treated with clozapine for at least 6 months were compared with 30 chronic schizophrenic patients treated with classic antipsychotic agents for the same length of time. Data on serum levels of cholesterol and triglycerides and on aggressive and suicidal behavior, as measured by the Overt Aggression Scale (OAS), were collected in both groups before treatment and 6 months later. A significant reduction in aggressive and suicidal behavior was noted in the clozapine-treated group but not in the classical antipsychotic-treated group. Clozapine treatment was associated with an elevation in serum triglyceride level, whereas classic antipsychotic treatment was associated with an increase in serum cholesterol level. We conclude that serum cholesterol level does not play a role in the clozapine-induced attenuation in aggressive and suicidal behavior in neuroleptic-resistant schizophrenic patients, though the accompanying elevation in triglycerides may be relevant to a behavioral effect.

Adolescent↗